Kinetic and structural data have revealed that chymotrypsin possesses an active site which is highly ionic. The reason for undertaking this research project is to investigate the electrostatic properties of the site. This will be accomplished by studying the ionic strength and dielectric effects on chymotrypsin-catalyzed hydrolyses. Since the ionic form of the site is pH dependent, the work will be done over a wide pH range using a variety of substates, i.e., peptides, esters and amides. In order to positively identify these groups, chemically modified chymotrypsins will also be employed. This will add an important dimension to the study, in that, it should indicate which ionic groups are catalytic or binding and which are required for the conformation of the site. The extent to which the active site of chymotrypsin is exposed to solvent has become highly controversial. The absolute assignment of the kenetic pKa values to the ionic groups responsible for catalytic activity depends upon the extent of solvent interaction. Therefore, studies, which determine the influence that changes in ionic strength and dielectric effects of the solvent have on these pKa values are an important contribution to understanding the mechanism of chymotrypsin catalysis.